Abstracts

RATIONALE:_ The incidence of seizures and epilepsy rises rapidly after age 60. Identified risk factors include stroke and Alzheimer disease (AD). We recently identified stroke following onset of AD symptoms as an independent risk factor for the occurrence of incident tonic-clonic seizures. Because little is known of the brain pathology present in patients with AD who develop seizures, we evaluated necropsy data obtained from a large dementia cohort under longitudinal observation. METHODS: We examined the occurrence of tonic-clonic seizures following onset of AD symptoms in 1302 patients with probable or possible AD followed longitudinally at the Alzheimer's Disease Research Center of Pittsburgh. To evaluate the brain pathologies related to seizure occurrence, we reviewed available brain necropsy results from cohort patients who had experienced a first tonic-clonic seizure during follow-up. RESULTS: A total of 33/1302 (2.5%) AD patients developed tonic-clonic seizures during mean follow-up of 40 (SD 32) months and mean AD symptom duration of 88 (SD 44, range 4-331) months. Necropsy results were available from 261/1302 of the AD group, and from 22/33 of those with incident seizures. Necropsy results in AD patients with seizures revealed that 20/22 (91%) had pathologically proven AD, 1/22 had striatonigral degeneration, and 1/22 had PSP. Of the 20 patients with proven AD, 7 had AD alone, 4 had AD plus stroke, 4 had AD plus cerebral amyloid angiopathy, 1 had AD plus stroke and amyloid angiopathy, 1 had AD plus Lewy bodies, 2 had AD plus Lewy bodies and amyloid angiopathy, and 1 had AD plus amyloid angiopathy and significant cerebral atherosclerosis. CONCLUSIONS: These findings indicate that tonic-clonic seizures occur in a small proportion of patients with probable/possible AD. Brain necropsy findings suggest that seizures occur in a minority of patients with pure AD, and are more likely to occur in the setting of concurrent AD and stroke or other vascular pathology such as amyloid angiopathy. These findings support prior reports indicating that stroke following the onset of AD symptoms is a significant risk factor for incident seizures in patients with probable AD.